Disruption of Sleep May Contribute to Many Symptoms of Mental Illness

cover-02-132x200Karen Gamble joined the Department of Psychiatry and Behavioral Neurobiology at UAB in September 2009, after completing her postdoctoral training at Vanderbilt University.  Dr. Gamble holds a Ph.D. in Behavioral Neuroscience and received a prestigious Pathway to Independence Award from the National Institutes of Health, for a project entitled “Integration of Photic and Nonphotic Signaling in the Circadian Pacemaker.”

The focus of Dr. Gamble’s research is the investigation of sleep timing controlled by the brain’s clock (circadian system). Clock disturbances can greatly disrupt sleep and are characteristic of many mental health disorders including depression and schizophrenia.  Studies have shown that disruption in the timing of sleep can worsen the symptoms of many psychiatric disorders.  Furthermore, the symptoms resulting from disrupted sleep timing, for example, in shift workers or during ‘jetlag’, can be mistaken for psychiatric illness in people who do not have a psychiatric disorder.  On a much broader scale, shift work has been associated with an increased risk of developing cardiovascular disease, metabolic and gastrointestinal disorders, depression, as well as cancer.  In fact, in an animal model of chronic jet lag, circadian researcher Alec Davidson, Ph.D. and colleagues at Morehouse Medical School have shown that geriatric animals had greatly increased mortality rates compared to un-shifted controls.  Dr. Gamble’s research aims to determine how genetic and environmental disruption of the circadian system can lead to mental illness and other medical problems, using animal models of clock-controlled sleep disturbances.

The brain’s master clock is located in a region called the suprachiasmatic nucleus (SCN) of the hypothalamus.  The clock synchronizes with the environment, for example with daylight, due to the activity of “clock” genes called Period1 and Period2. Clock gene activity can be measured in real-time using glowing reporter proteins from fireflies and jelly fish that are artificially linked to the clock genes. These reporters can be used to record electrical signals (the primary language of brain cells) and gene activity at the same time in individual living brain cells. Twenty-four hour gene activity continues for many months after culturing brain slices containing the SCN, and this property allows for examination of the chemical signals that are critical for clock function. Recently, Dr. Gamble and her colleagues demonstrated the importance of a well-known chemical signal in the SCN, gastrin releasing peptide, in the process of resetting the clock and activating clock genes.  In addition to light, other stimuli can also reset the clock, such as arousal and exercise.  In the future, she plans to use similar strategies to investigate how the clock’s cells interpret and respond to conflicting stimuli such as when exercise and light occur together.

In an effort to extend the basic knowledge of circadian rhythms to humans, Dr. Gamble has explored genetic and environmental predictors of adaptation to night-shift work in hospital nurses.  All of us who have benefited from nurse care in hospitals will be interested in how nurses adapt, or do not adapt, to shift work behaviorally and genetically.  In her research, Dr. Gamble and colleagues at Vanderbilt University identified five novel sleep strategies that nightshift nurses used for their days-off.  Nurses who used sleep deprivation in order to switch between day- and night-shifts were the most poorly adapted to night-shift.  In addition, this study showed that some genotypes of circadian clock genes are associated with alcohol and caffeine consumption, sleepiness, sleep duration, and tendency to be a night owl.  Finally, this research demonstrated genes can interact with the environment because some circadian genotypes only contributed to behavior under certain shift conditions.

At UAB, Dr. Gamble is collaborating with Dr. Rachel Fargason, Dr. Xiaohua Li, and Roberta May in a clinical trial exploring new treatments for people with attention deficit hyperactivity disorder (ADHD) with insomnia.  This collaborative group plans to test the idea that some ADHD patients experience insomnia because they have late clocks and are thus, night owls.  Insomnia worsens the symptoms of ADHD.  They expect treatment with a drug that enhances the effects of melatonin will reset the clock in these patients and improve their symptoms.

We are delighted to welcome Dr. Gamble to the Department and look forward to seeing interesting research developments from her laboratory on this important clinical problem.